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[硫氧还蛋白相互作用蛋白/核苷酸结合寡聚化结构域样受体蛋白3炎性小体在链脲佐菌素诱导的糖尿病大鼠坐骨神经中的表达]

[Expressions of Thioredoxin Interacting Protein/Nucleotide-binding Oligomerization Domain-like Receptor Protein 3 Inflammasome in the Sciatic Nerve of Streptozotocin-induced Diabetic Rats].

作者信息

Sun Qing, Wang Chao, Yan Bin, Shi Hu Xiao, Shi Yue, Qu Ling, Liang Chun Xiao

机构信息

Department of Traditional Chinese Medicine,PUMC Hospital,CAMS and PUMC,Beijing 100730,China.

出版信息

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2019 Dec 30;41(6):799-805. doi: 10.3881/j.issn.1000-503X.11468.

Abstract

To investigate the role of thioredoxin interacting protein(TXNIP)/ nucleotides-binding oligomerization domain-like receptor protein(NLRP)3 inflammasome in the sciatic nerve of streptozotocin(STZ)-induced diabetic rats. The diabetic rat model was established by single intraperitoneal injection of STZ.The rats with matched sex and age were taken as normal control group.The blood glucose and body weight were monitored.The mechanical withdrawal threshold was measured by von Frey filaments at 12 weeks after the model was established.At 12 weeks,the rats were sacrificed and the sciatic nerves were separated for Luxol fast blue staining,the expressions of TXNIP,NLRP3,caspase-1,and interleukin(IL)-1β were detected by immunohistochemistry and Western blot method,and the levels of IL-1β and IL-18 in serum were measured by enzyme-linked immunosorbent assay(ELISA). The expression of TXNIP protein in the sciatic nerve of diabetic rats was 3.78±0.08,which significantly increased than that in the normal control group(0.99±0.06)(=26.980,<0.0001).Compared with the normal control group(0.97±0.05),the expression of NLRP3 protein in the diabetic group(2.44±0.16)was significantly higher(=8.885,<0.0001).The expression of cleaved caspase-1 was 4.45±0.19 in the diabetic group and 1.08±0.06 in the normal control group,and the difference was significant(=16.900,<0.0001).The expression of IL-1β protein in the diabetic group(4.50±0.16)was significantly higher than that(1.19±0.08)in the normal control group(=18.630,<0.0001).Compared with the normal control group,the levels of IL-1β [(110.50±8.80)pg/ml (17.97±3.18)pg/ml,=9.892,<0.0001] and IL-18 [(591.70±8.78)pg/ml (160.70±8.33)pg/ml,=35.620,<0.0001] in the serum of diabetic rats significantly increased. The pathogenesis of diabetic peripheral neuropathy may be related to increased expression of TXNIP,activation of NLRP3 inflammasome,and downstream inflammation,which may provide a new target for diabetic peripheral neuropathy therapy.

摘要

探讨硫氧还蛋白相互作用蛋白(TXNIP)/核苷酸结合寡聚化结构域样受体蛋白(NLRP)3炎性小体在链脲佐菌素(STZ)诱导的糖尿病大鼠坐骨神经中的作用。通过单次腹腔注射STZ建立糖尿病大鼠模型。选取性别和年龄匹配的大鼠作为正常对照组。监测血糖和体重。在模型建立后12周,用von Frey细丝测量机械性撤针阈值。12周时,处死大鼠并分离坐骨神经进行Luxol固蓝染色,采用免疫组织化学和蛋白质印迹法检测TXNIP、NLRP3、半胱天冬酶-1(caspase-1)和白细胞介素(IL)-1β的表达,并用酶联免疫吸附测定(ELISA)法检测血清中IL-1β和IL-18的水平。糖尿病大鼠坐骨神经中TXNIP蛋白的表达为3.78±0.08,显著高于正常对照组(0.99±0.06)(t=26.980,P<0.0001)。与正常对照组(0.97±0.05)相比,糖尿病组NLRP3蛋白的表达(2.44±0.16)显著升高(t=8.885,P<0.0001)。糖尿病组裂解的caspase-1的表达为4.45±0.19,正常对照组为1.08±0.06,差异有统计学意义(t=16.900,P<0.0001)。糖尿病组IL-1β蛋白的表达(4.50±0.16)显著高于正常对照组(1.19±0.08)(t=18.630,P<0.0001)。与正常对照组相比,糖尿病大鼠血清中IL-1β[(110.50±8.80)pg/ml比(17.97±3.18)pg/ml,t=9.892,P<0.0001]和IL-18[(591.70±8.78)pg/ml比(160.70±8.33)pg/ml,t=35.620,P<0.0001]水平显著升高。糖尿病周围神经病变的发病机制可能与TXNIP表达增加、NLRP3炎性小体激活及下游炎症反应有关,这可能为糖尿病周围神经病变的治疗提供新靶点。

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